The aim of this study was to test the application of an in situ–formed synthetic polyethylene glycol (PEG) as a biodegradable membrane with a variety of graft materials and hyperbaric oxygen (HBO) for enhanced bone regeneration. Critical-sized rabbit calvarial defects were created in bilateral parietal bones. Group 1 served as a control with unfilled defects, Group 2 had defects filled with morcelized autogenous bone, and Group 3 had defects filled with biphasic calcium phosphate. One defect was protected PEG membrane and half the animals were subjected to HBOT treatment. The unsupported membrane didn’t produce the desired bone regeneration in the unfilled and bone grafted groups. HBO didn't ameliorate the bone grafted or ceramic filled defects over the 6-week time period. Caution is recommended with the membrane over unsupported defects. Future assessments with HBO should be completed at the 12-week time point.

In this dissertation, small and large NaCl particle-derived surfaces (Ra > 40 microns) were generated on 2D Zn materials, and the surfaces were carefully studied concerning topography, corrosion behavior, and bone cell compatibility. Increases in surface roughness accelerated the corrosion rate, and cell viability was maintained. This method was then extended to 3D porous scaffolds prepared by a hybrid AM/casting technique. The scaffolds displayed a near-net shape, an interconnected pore structure, increasing porosity paralleled to an increased corrosion rate, an ability to support cell growth, and powerful antibacterial properties. Lastly, nano/micro (Rz 0.02–1 microns) topographies were generated on 2D Zn materials, and the materials were comprehensively studied with special attention devoted to corrosion behavior, biocompatibility, osteogenic differentiation, immune cell response, hemocompatibility, and antibacterial performance. For the first time, the textured nonhemolytic surfaces on Zn were shown to direct cell fate, and the micro-textures promoted bone cell differentiation and directed immune cells away from an inflammatory phenotype.

O objetivo desta pesquisa em humanos é avaliar clínica e histologicamente os resultados obtidos de implantes instalados imediatamente à exodontia (Grupo 1) e de implantes tardios instalados em alvéolos regenerados (Grupo 2). Nos dois grupos, matriz óssea liofilizada xenógena foi utilizada associada à membrana de colágeno bovino reabsorvível e/ou membrana não reabsorvível de politetrafluoretileno expandido (PTFEe), seguindo-se os princípios da Regeneração Tecidual Guiada. Vinte pacientes, dez de cada grupo, foram acompanhados clinicamente durante 10 anos, submetidos a análises clínicas em intervalo de 1, 3, 5 e 10 anos e à análise histológica do osso alveolar neoformado após 6 meses da enxertia. Os pacientes foram avaliados clinicamente quanto à presença de sinais ou sintomas de doença periodontal através de sondagem. A avaliação histológica das lâminas previamente confeccionadas foi realizada através de classificação qualitativa de formação óssea e de possíveis remanescentes de biomaterial. Os aspectos clínicos (profundidade de sondagem e índice de sangramento marginal) nos Grupos 1 e 2 foram semelhantes e, através de uma análise subjetiva, pôde-se verificar que os pacientes dos Grupos 1e 2 realizaram uma boa manutenção da higiene bucal promovendo, dessa maneira, um índice insignificante de presença de sinais e sintomas de doença periodontal. Quanto às análises histológicas, os Grupos 1 e 2 se equiparam. Por essa razão, a apresentação da análise histológica da região com neoformação óssea, depois do período determinado, revelou o grau de maturação do osso remodelado na superfície perimplantar onde foi colocado o enxerto xenógeno, condizente com o quadro esperado pela osseointegração. Os enxertos xenogênicos associados à membrana possibilitam a manutenção do rebordo para a colocação de implantes e reabilitação protética, sejam no mesmo momento da extração e colocação imediata dos implantes ou em casos de preenchimento de alvéolos após exodontia e instalação tardia de implantes. / The aim of this research is to evaluate the clinical and histological findings of installed implants immediately after exodontics (Group 1) and later after the alveolus regeneration (Group 2). In both groups, xenogeneous lyophilized bone matrix was used in association with resorbable bovine collagen membrane and/or nonresorbable expanded politetrafluoretane membrane (PTFE - e) following the guided tissue regeneration principles. 20 patients, 10 in each group, were clinically followed during 10 years, submitted to clinical analysis during intervals of 1, 3, 5 and 10 years, and to histological analysis of the neoformed alveolar bone after 6 months of grafting. The patients were clinically evaluated as for signs and symptoms of periodontal disease by means of probing depth. The histological evaluation of the previously prepared laminae were performed after qualitative classification of bone formation and of possible biomaterial remnants. The clinical aspects (probing of depth and marginal bleeding index) in groups 1 and 2 were similar. After a subjective analysis, it could be verified that the patients in both groups performed an acceptable maintenance of oral hygiene, promoting, in such way, an insignificant index of periodontal disease signs and symptoms. The histological analysis of both groups were equivalent. For this reason, the histological analysis of the neoformed bone region after the determined period revealed the degree of maturation of the remodelated bone at the periimplant surface where the xenogeneous graft was placed, consistent with the expected osseointegration scenario. The xenogenic grafts associated with membranes perform the maintenance of the alveolar ridge for implant installation and prosthetic rehabilitation, either immediately after extraction or later after extraction and alveolus filling.

No description available.

No description available.

Recombinant human bone morphogenetic proteins (rhBMPs) are increasingly used for reconstructing bony defects, fracture non-unions, and augmenting existing bone volumes. For the numerous patients taking bisphosphonates, the impact of prior bisphosphonate treatment on rhBMP bone induction is not well understood. Objective: to evaluate the effect of the prior treatment with zoledronate on rhBMP induced bone formation in mice. Methods: 42 mice were pre-treated with 0, 2, and 20 µg of zoledronate/mouse. The osteoinductive activity of a bioimplant, containing rhBMP-2, was assessed using the mouse muscle pouch assay, and analyzed with micro CT and histology. Results: micro CT demonstrated that BMP bioimplants placed in mice pretreated with 20 µg of zoledronate, formed bony ossicles of greater volume but reduced bone density compared to controls. Histologically, the heterotopic ossicles from the 20 µg group consisted of more immature bone than those from the other groups. Conclusion: bone induced by rhBMP-2 in mice pre-treated with a high concentration of zoledronate was immature as evidenced by radiographic and histologic appearance.

Recombinant human bone morphogenetic proteins (rhBMPs) are increasingly used for reconstructing bony defects, fracture non-unions, and augmenting existing bone volumes. For the numerous patients taking bisphosphonates, the impact of prior bisphosphonate treatment on rhBMP bone induction is not well understood. Objective: to evaluate the effect of the prior treatment with zoledronate on rhBMP induced bone formation in mice. Methods: 42 mice were pre-treated with 0, 2, and 20 µg of zoledronate/mouse. The osteoinductive activity of a bioimplant, containing rhBMP-2, was assessed using the mouse muscle pouch assay, and analyzed with micro CT and histology. Results: micro CT demonstrated that BMP bioimplants placed in mice pretreated with 20 µg of zoledronate, formed bony ossicles of greater volume but reduced bone density compared to controls. Histologically, the heterotopic ossicles from the 20 µg group consisted of more immature bone than those from the other groups. Conclusion: bone induced by rhBMP-2 in mice pre-treated with a high concentration of zoledronate was immature as evidenced by radiographic and histologic appearance.

Large infected bone defects (IBD) are very complicated to treat due to their high variability; they often require multiple procedures. Bone autografts are the gold standard for treatment but have several drawbacks, such as a need for a second surgery site, limited grafting material, and donor site morbidity. The objective of this research was to develop a moldable synthetic bone grafting material capable of releasing both antimicrobial and osteogenic drugs over a clinically relevant time course for the treatment of IBDs. Current treatment methods for large IBDs require two separate procedures to treat the bone defect and the infection. This research sought to combine these two procedures into one implantable composite bone graft substitute for the treatment IBDs. To begin, the degradation and mechanical properties of the calcium sulfate (CS) based composite material were evaluated for different compositions. Next, the controlled drug release profiles from the composite was achieved by using a shell and core system incorporating poly(lactic-co-glycolic acid) microspheres (PLGAms). The release of vancomycin from the shell began immediately and continued over the course of 6 weeks, while the release of simvastatin from the core was delayed before being released over 4 weeks. Next, an infected, critically-sized rat femoral defect model was used to test different treatment methods with and without the composite bone graft substitute. Animals treated with locally released antibiotics had survivorship rates 24% higher than those treated with systemic antibiotics, and animals that received both antibiotics and an osteogenic drug had an increased amount of bone formation at 12 weeks compared to controls. Finally, several different anti-biofilm agents were evaluated for their ability to inhibit and/or disrupt the growth of Staphylococcus aureus (S. aureus) biofilms in vitro. Lysostaphin was the only drug investigated that was able to both inhibit and disrupt S. aureus biofilms. Furthermore, lysostaphin encapsulated into PLGAms maintained its bioactivity and may be useful for future incorporation into biofilm-combating materials. The bone grafting material developed here can be used to locally deliver drugs in a temporally controlled manner to reduce the number of procedures necessary for the treatment of complex IBDs.

Submitted by JÚLIO MACIEL SANTOS DE ARAÚJO null (juliovagga@hotmail.com) on 2016-01-27T00:08:21Z No. of bitstreams: 1 TESE Capa Dura Pos Defesa PDF.pdf: 76207614 bytes, checksum: cfa10f70db7d1eab06980724a3b9a277 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-01-28T13:57:32Z (GMT) No. of bitstreams: 1 araujo_jms_dr_araca.pdf: 76207614 bytes, checksum: cfa10f70db7d1eab06980724a3b9a277 (MD5) / Made available in DSpace on 2016-01-28T13:57:32Z (GMT). No. of bitstreams: 1 araujo_jms_dr_araca.pdf: 76207614 bytes, checksum: cfa10f70db7d1eab06980724a3b9a277 (MD5) Previous issue date: 2015-12-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Proposição: O objetivo desse trabalho foi avaliar a interface enxerto/leito receptor de um bloco sintético bifásico, composto de 60% de hidroxiapatita e 40% de beta tricálcio fosfato (β-TCP) por meio de análise histológica, histométrica e imunoistoquímica. Materiais e métodos: Foram utilizados 12 coelhos albinus que foram submetidos à cirurgia de enxerto ósseo aposicional em bloco para ganho em espessura. O enxerto autógeno foi removido da tíbia com o auxílio de uma broca trefina de 8 mm e parafusado na mandíbula esquerda, enquanto o bloco teste bifásico, composto de 60% de HA e 40% de β-TCP, foi parafusado na mandíbula direita. Os animais sofreram eutanásia após 2 e 8 semanas do procedimento cirúrgico e a peça foi removida para processamento e análises. Os resultados obtidos tiveram sua normalidade testada para definir o teste estatístico indicado. Resultados: Na análise histométrica, podemos observar que o grupo autógeno demonstrou maiores taxas de neoformação óssea nos dois tempos estudados quando comparados ao grupo do biomaterial, demonstrando uma diferença estatisticamente significativa. Quando comparamos os tempos estudados em cada material, o grupo autógeno teve um aumento considerável da segunda para a oitava semana, porem não foi encontrada diferenças estatisticamente significativas. O grupo biomaterial não teve um aumento significativa de neoformação óssea durante o período de reparo. Na imunoistoquímica, com relação ao tempo, podemos observar que a enzima TRAP mostrou maior manifestação no período de 2 semanas do que no período de 8 semanas considerando os dois materiais estudados. No quesito material, a proteína OC mostrou mais evidente no grupo autógeno de uma forma geral. Quando se avaliou material e tempo em cada proteína isoladamente não foram encontradas diferenças estatisticamente significativas. Conclusão: O bloco testado manteve valores de neoformação óssea inferiores ao bloco controle, demonstrando menor potencial de integração. A sua composição se mostrou confiável para reconstruções alveolares em espessura com intuito de preenchimento. Mais estudos com diferentes modelos de estudo e métodos devem ser analisados, de preferência associados a componentes celulares com o intuito de acharmos um substituto ideal para enxertos autogénos. / Proposition: The purpose of this study was to evaluate the interface graft / recipient bed of a two-phase synthetic block, consisting of 60 % hydroxyapatite and 40 % beta tricalcium phosphate (β -TCP) by histological analysis, histometric and immunohistochemistry. Methods: We used 12 albinus rabbits that underwent appositional bone graft surgery block to gain in thickness. The autogenous graft was removed from the tibia with the aid of a trephine drill 8 mm and screwed into the left jaw, while the biphasic pattern block, composed of 60 % HA and 40% β -TCP, was screwed in the right jaw. The animals were euthanized after 2 and 8 weeks of surgery and the piece was removed for processing and analysis. The results were tested for normality define the statistical test indicated. Results: In histometric analysis, we can see that the autogenous group showed higher rates of bone formation in both times studied compared to the biomaterial group, demonstrating a statistically significant difference. When we compare the times studied in each material, the autogenous group had a significant increase from the second to the eighth week, however, there was no statistically significant differences. The biomaterial group remained during the repair period. In immunohistochemistry, with respect to time, we can see that the TRAP enzyme showed greater expression in the two weeks period than 8 weeks considering the two materials studied. In the item material, OC protein was more evident in the group of autogenic general. When assessing the material and time each protein alone were no statistically significant differences. Conclusion: The block kept tested values of bone formation below the control block, showing less potential for integration. Its composition has proven reliable for alveolar reconstruction in thickness to fill order. Further studies with different study models and methods to be analyzed, preferably associated with cellular components in order to we find an ideal substitute for autogenous grafts.

O objetivo desta pesquisa em humanos é avaliar clínica e histologicamente os resultados obtidos de implantes instalados imediatamente à exodontia (Grupo 1) e de implantes tardios instalados em alvéolos regenerados (Grupo 2). Nos dois grupos, matriz óssea liofilizada xenógena foi utilizada associada à membrana de colágeno bovino reabsorvível e/ou membrana não reabsorvível de politetrafluoretileno expandido (PTFEe), seguindo-se os princípios da Regeneração Tecidual Guiada. Vinte pacientes, dez de cada grupo, foram acompanhados clinicamente durante 10 anos, submetidos a análises clínicas em intervalo de 1, 3, 5 e 10 anos e à análise histológica do osso alveolar neoformado após 6 meses da enxertia. Os pacientes foram avaliados clinicamente quanto à presença de sinais ou sintomas de doença periodontal através de sondagem. A avaliação histológica das lâminas previamente confeccionadas foi realizada através de classificação qualitativa de formação óssea e de possíveis remanescentes de biomaterial. Os aspectos clínicos (profundidade de sondagem e índice de sangramento marginal) nos Grupos 1 e 2 foram semelhantes e, através de uma análise subjetiva, pôde-se verificar que os pacientes dos Grupos 1e 2 realizaram uma boa manutenção da higiene bucal promovendo, dessa maneira, um índice insignificante de presença de sinais e sintomas de doença periodontal. Quanto às análises histológicas, os Grupos 1 e 2 se equiparam. Por essa razão, a apresentação da análise histológica da região com neoformação óssea, depois do período determinado, revelou o grau de maturação do osso remodelado na superfície perimplantar onde foi colocado o enxerto xenógeno, condizente com o quadro esperado pela osseointegração. Os enxertos xenogênicos associados à membrana possibilitam a manutenção do rebordo para a colocação de implantes e reabilitação protética, sejam no mesmo momento da extração e colocação imediata dos implantes ou em casos de preenchimento de alvéolos após exodontia e instalação tardia de implantes. / The aim of this research is to evaluate the clinical and histological findings of installed implants immediately after exodontics (Group 1) and later after the alveolus regeneration (Group 2). In both groups, xenogeneous lyophilized bone matrix was used in association with resorbable bovine collagen membrane and/or nonresorbable expanded politetrafluoretane membrane (PTFE - e) following the guided tissue regeneration principles. 20 patients, 10 in each group, were clinically followed during 10 years, submitted to clinical analysis during intervals of 1, 3, 5 and 10 years, and to histological analysis of the neoformed alveolar bone after 6 months of grafting. The patients were clinically evaluated as for signs and symptoms of periodontal disease by means of probing depth. The histological evaluation of the previously prepared laminae were performed after qualitative classification of bone formation and of possible biomaterial remnants. The clinical aspects (probing of depth and marginal bleeding index) in groups 1 and 2 were similar. After a subjective analysis, it could be verified that the patients in both groups performed an acceptable maintenance of oral hygiene, promoting, in such way, an insignificant index of periodontal disease signs and symptoms. The histological analysis of both groups were equivalent. For this reason, the histological analysis of the neoformed bone region after the determined period revealed the degree of maturation of the remodelated bone at the periimplant surface where the xenogeneous graft was placed, consistent with the expected osseointegration scenario. The xenogenic grafts associated with membranes perform the maintenance of the alveolar ridge for implant installation and prosthetic rehabilitation, either immediately after extraction or later after extraction and alveolus filling.